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Biomedical subjects

Chun Zhang

Publications and source records attributed to Chun Zhang.

At least 37 records · Page 2Linked to original sources

Utilization of double-orifice valve plasty in correction of atrioventricular septal defect.

BACKGROUND: Atrioventricular valve regurgitation represents the principal indication for reoperation after repair of atrioventricular septal defect. Deciding how to correct atrioventricular valve regurgitation is challenging in some cases because of the complexity of the anatomic features. This report deals with our surgical experience in using a double-orifice valve plasty technique in cases with atrioventricular septal defect. METHODS: From August 2002 to August 2004, 8 patients underwent double-orifice valve plasty in surgical correction of atrioventricular septal defect. Anatomic types were partial (6 patients), intermediate (1 patient), and complete (1 patient). After the mitral cleft was closed, moderate to severe atrioventricular valve regurgitation was still present in these patients. Double-orifice valve plasty was used in the mitral valve in 7 patients and in the tricuspid valve in 1. RESULTS: No hospital deaths or postoperative morbidity occurred. The follow-up ranged from 6 months to 30 months (median, 14.4 months). No or trivial atrioventricular valve regurgitation was found in 6 patients and mild atrioventricular valve regurgitation was present in 2. CONCLUSIONS: Double-orifice valve plasty is an easy and effective additional procedure for children and for adult patients who have moderate or severe atrioventricular valve regurgitation after repair of atrioventricular septal defect.

Abnormalities, Multiple↗

Edge-to-edge tricuspid valve repair: an adjuvant technique for residual tricuspid regurgitation.

BACKGROUND: Tricuspid regurgitation is a very common valve disease. Significant morbidity and mortality is associated with tricuspid valve replacement and tricuspid valve plasty is still a preferred choice. Because of the abnormality of valve and subvalvular apparatus, tricuspid valve plasty is sometimes complicated and associated with suboptimal results. This report deals with our surgical experience in using edge-to-edge valve plasty technique in cases with severe residual tricuspid regurgitation. METHODS: From April 2001 to November 2004, 15 patients with severe residual tricuspid regurgitation underwent edge-to-edge tricuspid valve plasty. The etiology of tricuspid regurgitation was secondary to rheumatic heart disease in 5 cases, secondary to congenital heart disease in 5 cases, to congenital tricuspid valve dysplasia in 1 case, and to posttraumatic and degenerative disease in 2 cases, respectively. After tricuspid valve repair was performed with traditional methods, severe tricuspid regurgitation was still present. Edge-to-edge tricuspid valve plasty was used in these patients. RESULTS: There was 1 hospital death. No or trivial tricuspid regurgitation was found in 6 cases, and mild tricuspid regurgitation was present in 9 cases after operation. The follow-up ranged from 8 to 51 months (median, 25.3). Trivial to mild tricuspid regurgitation was present in 12 cases and mild to moderate tricuspid regurgitation in 2 cases. CONCLUSIONS: Edge-to-edge tricuspid valve plasty is an effective adjuvant procedure for patients who have severe residual tricuspid regurgitation.

Adolescent↗

Induction of gynogenesis in Japanese crucian carp (Carassius cuvieri).

Diploid gynogenesis was induced in Japanese crucian carp (Carassius cuvieri) eggs using UV-irradiated genetically inactive spermatozoa from mirror carp (Cyprinus carpio L.) or blunt snout bream (Megalobrama amblycephala), with or without cold shock. The optimal radiation dosage was 4,200 mJ/cm2 and 3,600 mJ/cm2 for mirror carp and blunt snout bream sperm, respectively. At this dosage and without cold shock, the yields were (32.4 +/- 3.3)% vs. (33.8 +/- 1.4)% gynogenetic haploids and (0.7 +/- 0.3)% vs. (0.5 +/- 0.3)% hybrid diploids, respectively. At the optimal UV dosage but with cold shock (2 min after fertilization, 0-4 degrees C for 40 min), the hatching rates were (27.8 +/- 2.1)% and (29.4 +/- 3.3)%, respectively. From hatching to feeding, (15.7 +/- 3.4)% and (23.6 +/- 4.1)% normal gynogenetic diploids were recorded, respectively. Survival of normal gynogenetic diploids was 56% out of the hatched fry when using irradiated spermatozoa of mirror carp, which was lower than that (up to 80%) when using irradiated spermatozoa of blunt snout bream. This indicated that the sperm of blunt snout bream, with distant genetic relation to the maternal Japanese crucian carp, was more effective than that of mirror carp to induce diploid gynogenesis. The nature of the gynogenetic progeny was identified with external appearance, chromosome number and gonad structure. The presence of only females in gynogenetic progeny probably suggested XX genotype in the female Japanese crucian carp. The gynogenetic diploids have potential values such as faster growth and stronger disease resistance than the normal Japanese crucian carp. All gynogenetic progeny possessed 100 chromosomes whereas all J x B crosses were triploid with 124 chromosomes. The formation of the new triploid hybrids in J x B crosses may be useful in aquaculture.

Animals↗

A gene delivery approach for antimicrobials: expression of defensins.

INTRODUCTION: Peptide antibiotics as new therapeutic agents are becoming a popular option to investigate due to their broad bacterial target selectivity and limited resistance problems. Although attractive, these new drug candidates have several limitations including low potency and delivery issues which face all peptides/proteins. METHODS: In this study, we designed a plasmid expression system for human beta defensin 3. This sequence was cloned from a human epithelial lung cell into a CMV driven expression cassette. This expression plasmid was then evaluated for its ability to produce human-beta defensin 3 with the use of the non-viral transfection agent, polyethylenimine (PEI). RESULTS: The results indicate the expression cassette was transcriptionally active in HEK 293 cells, as measured by RT-PCR and that a beta defensin peptide was produced by the cells as confirmed by Western blot. The biological activity of the peptide was confirmed against both gram negative E. coli and gram positive Bacillus species using in vitro screening. CONCLUSION: Both the cultured media as well as the transfected cell lysate demonstrated biological activity demonstrating the peptide is also secreted.

Anti-Bacterial Agents↗

Inhibition of ethanol-induced toxicity by tanshinone IIA in PC12 cells.

AIM: To observe the effects of tanshinone IIA (Tan IIA) on the neurotoxicity induced by ethanol in PC12 cells and to explore its protective role. METHODS: PC12 cell survival was measured by MTT assay. The formation of reactive oxygen species (ROS) and lactate dehydrogenase (LDH) release were detected by 2',7'-dichlorofluorescin (DCF) fluorescence and calorimetric method, respectively. The percentage of cell apoptosis was monitored by flow cytometry. The expression of p53 was detected by immuno-fluorescence and flow cytometry. RESULTS: Ethanol significantly impaired the survival of PC12 cells as demonstrated by MTT assay. Ethanol also induced significant ROS formation and increased LDH release. Pre-incubation with Tan IIA in the culture medium significantly reversed these changes. Ethanol caused cell apoptosis and the upregulation of p53 protein. The anti-apoptosis effects of Tan IIA on ethanol-induced toxicity were accompanied by the downregulation of pro-apoptotic p53 protein expression. CONCLUSION: Tan IIA can protect neurons from apoptosis and might serve as a potential therapeutic drug for neurological disorders induced by ethanol.

Abietanes↗

Inhibitory effect of triptolide on lymph node metastasis in patients with non-Hodgkin lymphoma by regulating SDF-1/CXCR4 axis in vitro.

AIM: To investigate the antiproliferative effect of triptolide on B-NHL cell line Raji cells, to study its effect on lymph node metastasis in patients with non-Hodgkin's lymphoma (NHL) in vitro, and to explore the underlying mechanism regulating SDF-1/CXCR4 axis. METHODS: The effects of triptolide on the growth of Raji cells were studied by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay. The effects of triptolide on SDF-1 mRNA expression in lymph node stromal cells from patients with NHL were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). The effects of triptolide on CXCR4 expression on lymphoma cells freshly isolated from the lymph nodes of these patients were studied by flow cytometric analysis. Chemotaxis assays were performed to observe the effects of triptolide on migration of primary lymphoma cells towards recombinant human SDF-1 alpha (rhSDF-1 alpha) or cultured lymph node stromal cells in vitro. RESULTS: Triptolide inhibited the proliferation of B-NHL cell line Raji cells in a dose- and time-dependent manner with a 24-h IC50 value of 43.06 nmol/L and a 36-h IC50 value of 25.08 nmol/L. The expression of SDF-1alpha mRNA in lymph node stromal cells obtained from patients with NHL was decreased after treatment by triptolide at concentrations of 25 and 50 nmol/L for 24 h. Flow cytometry analysis showed that the CXCR4 expression on primary lymphoma cells were downregulated gradually in a dose-dependent manner following triptolide treatment. Chemotaxis assays revealed that the migration of freshly isolated lymphoma cells towards either rhSDF-1 or cultured lymph node stromal cells was markedly inhibited by the addition of triptolide in vitro, and the inhibition was dose-dependent. CONCLUSION: Triptolide can inhibit the proliferation of B-NHL cell line Raji cells. Moreover, triptolide is able to inhibit the migration of lymphoma cells via lymph nodes in vitro. The potential antitumor mechanisms of triptolide are related to the antiproliferative effect and the blockage of SDF-1/CXCR4 axis.

Antineoplastic Agents, Alkylating↗

Intrapulmonary channel for one-stage correction of aortic arch obstruction.

There are several methods of surgical repair of aortic coarctation or interruption; the optimal technique is still controversial. The purpose of this study was to assess a new surgical method: intrapulmonary channel for one-stage repair of aortic coarctation or interruption associated with intracardiac anomalies. Between 1993 and 1995, 4 patients with aortic coarctation or interruption and intracardiac anomalies received one-stage surgical correction. Their ages ranged from 5 to 26 years (mean, 16 years). The aortic arch lesions were preductal coarctation in 2, and type B interruption in 2. Coexisting anomalies consisted of patent ductus arteriosus in 4, ventricular septal defect in 3, and aortopulmonary window in 1. An intrapulmonary channel was constructed in all patients, and co-existing anomalies were corrected simultaneously. There was no hospital death or late mortality. A cerebral complication occurred in one patient because of air embolism. Mean follow-up was 9.5 years (range, 8.5-11.5 years). There was no evidence of recoarctation or late aneurysm formation. For selected patients with aortic coarctation or interruption and intracardiac anomalies, an intrapulmonary channel might be an option for one-stage correction.

Adolescent↗

[A study on the karyotype, C-banding and Ag-NORs in Rana nigromaculata].

The chromosome samples of Rana nigromaculata were prepared by peripheral blood lymphocyte cultured in vitro. Karyotype, C-banding and silver-staining nucleolus organizer regions (Ag-NORs) were observed on chromosomes samples. The result showed that: (1) the chromosome number of Rana nigromaculata is 26 (2n=26), i.e., 10 large and 16 small chromosomes, the large chromosomes are matched into 5 homologous pairs and small chromosomes are matched into 8 homologous pairs, and further indicates the karyotype of Rana nigromaculata is bi-modal; (2) Metaphases of female and male were observed separately, the chromosome of No.11 has a pronounced secondary constriction in the middle of long arms. But the position of secondary constriction in the aberrant type individuals is in the middle of long arms of the No.8; (3) it has only one obvious C-banding close to the telomere, which is located in the long arms of the No.5; (4) The chromosome No.11 is a pair of homologous chromosomes with Ag-NORs, and the position of Ag-NORs in female and male is identical.

Animals↗

[Phase II clinical trial of home-produced Nedaplatin in treating advanced esophageal carcinoma].

BACKGROUND & OBJECTIVE: Nedaplatin is a second-generation anticancer drug containing organic platinum. Clinical researches in overseas showed that Nedaplatin is an anticancer drug with broad spectrum and high efficiency, especially in treating esophageal carcinoma. But the therapeutic efficacy and toxicity of home-produced Nedaplatin in China are unclear. This study was to evaluate the efficacy of home-produced Nedaplatin in China on esophageal carcinoma, and observe its toxicity. METHODS: A multi-center, phase II, prospective clinical trial was conducted. Naive patients with esophageal carcinoma were enrolled and randomized into trial group and control group. The patients in trial group were treated with home-produced Nedaplatin plus 5-fluorouracil (5-FU); the patients in control group were treated with cisplatin (DDP) plus 5-FU. RESULTS: A total of 52 patients were enrolled: 30 in trial group, and 22 in control group. For trial group, therapeutic efficacy was evaluable in 27 cases, and toxicity was evaluable in all cases; for control group, therapeutic efficacy and toxicity were evaluable in all cases. The response rate was significantly higher in trial group than in control group (29.62% vs. 22.72%, P<0.05). The complete remission (CR) rates were 18.51% in trial group and 4.55% in control group. When considering myelosuppression, the occurrence rate of anemia was similar in the 2 groups; but the occurrence rates of neutropenia and thrombocytopenia were higher in trial group than in control group, especially for grade III-IV thrombocytopenia (20.68% vs. 0%, P<0.01). The occurrence rate of gastrointestinal reaction was lower in trial group than in control group. There were no significant differences in hepatotoxicity, renal toxicity, heart toxicity, peripheral nerve toxicity, and alopecia between the 2 groups. CONCLUSIONS: Nedaplatin is an effective platinum drug for esophageal carcinoma. The treatment efficacy of Nedaplatin plus 5-FU regimen is better than that of DDP plus 5-FU regimen. It has a good clinical tolerance. The main toxicity is myelosuppression, and thrombocytopenia is predominant.

Adult↗

A genome-wide linkage analysis of alcoholism on microsatellite and single-nucleotide polymorphism data, using alcohol dependence phenotypes and electroencephalogram measures.

The Collaborative Study on the Genetics of Alcoholism (COGA) is a large-scale family study designed to identify genes that affect the risk for alcoholism and alcohol-related phenotypes. We performed genome-wide linkage analyses on the COGA data made available to participants in the Genetic Analysis Workshop 14 (GAW 14). The dataset comprised 1,350 participants from 143 families. The samples were analyzed on three technologies: microsatellites spaced at 10 cM, Affymetrix GeneChip Human Mapping 10 K Array (HMA10K) and Illumina SNP-based Linkage III Panel. We used ALDX1 and ALDX2, the COGA definitions of alcohol dependence, as well as electrophysiological measures TTTH1 and ECB21 to detect alcoholism susceptibility loci. Many chromosomal regions were found to be significant for each of the phenotypes at a p-value of 0.05. The most significant region for ALDX1 is on chromosome 7, with a maximum LOD score of 2.25 for Affymetrix SNPs, 1.97 for Illumina SNPs, and 1.72 for microsatellites. The same regions on chromosome 7 (96-106 cM) and 10 (149-176 cM) were found to be significant for both ALDX1 and ALDX2. A region on chromosome 7 (112-153 cM) and a region on chromosome 6 (169-185 cM) were identified as the most significant regions for TTTH1 and ECB21, respectively. We also performed linkage analysis on denser maps of markers by combining the SNPs datasets from Affymetrix and Illumina. Adding the microsatellite data to the combined SNP dataset improved the results only marginally. The results indicated that SNPs outperform microsatellites with the densest marker sets performing the best.

Alcoholism↗

Description of the data from the Collaborative Study on the Genetics of Alcoholism (COGA) and single-nucleotide polymorphism genotyping for Genetic Analysis Workshop 14.

The data provided to the Genetic Analysis Workshop 14 (GAW 14) was the result of a collaboration among several different groups, catalyzed by Elizabeth Pugh from The Center for Inherited Disease Research (CIDR) and the organizers of GAW 14, Jean MacCluer and Laura Almasy. The DNA, phenotypic characterization, and microsatellite genomic survey were provided by the Collaborative Study on the Genetics of Alcoholism (COGA), a nine-site national collaboration funded by the National Institute of Alcohol and Alcoholism (NIAAA) and the National Institute of Drug Abuse (NIDA) with the overarching goal of identifying and characterizing genes that affect the susceptibility to develop alcohol dependence and related phenotypes. CIDR, Affymetrix, and Illumina provided single-nucleotide polymorphism genotyping of a large subset of the COGA subjects. This article briefly describes the dataset that was provided.

Alcoholism↗

[Role of connective tissue growth factor in human renal tubular epithelial cell transdifferentiation in vitro].

OBJECTIVE: To observe the effect of connective tissue growth factor (CTGF) on the transdifferentiation of human renal tubular epithelial cells and to explore the influence of CTGF antisense oligodeoxynucleotide (ASODN) transfection on the transdifferentiation process induced by transforming growth factor-beta1 (TGF-beta1). METHODS: Human renal tubular epithelial cells of the strain HKC were cultured and divided into 3 groups: (1) negative control group, (2) low dose CTGF group, treated with recombinant human CTGF (rhCTGF) with the terminal concentration of 2.5 microg/L, and (3) high dose CTGF group, treated with rhCTGF with the terminal concentration of 5.0 microg/L). To evaluate the contribution of CTGF to the transdifferentiation induced by TGF-beta1, Another HKC cells were divided into 4 groups: (1) untreated control group (Group C), (2) Group T, stimulated by TGF-beta1 (10.0 microg/L), (3) Group S, stimulated by sense ODN transfection + TGF-beta1 (10.0 microg/L), and (4) Group A, stimulated by antisense ODN transfection + TGF-beta1 (10.0 microg/L). RT-PCR was used to detect the mRNA expression of alpha-smooth muscle actin (alpha-SMA) and collagen type IV (col IV) mRNA. Indirect immunofluorescence assay and flow cytometry were used to assess the level of intracellular alpha-SMA protein. ELISA was used to determine the concentration of col IV in the media. RESULTS: The normal HKC cells were round and the HKC cells stimulated with rhCTGF became elongated. Upon the stimulation of different concentrations of rhCTGF, the expression of alpha-SMA mRNA increased markedly (both P < 0.01), while the mRNA expression of collagen type IV gene was down-regulated significantly (both P < 0.01). The percentage of alpha-SMA positive cells was significantly higher in the stimulated groups than that in negative control with significant difference among any 2 groups (38.9%, 65.5% vs. 2.4% respectively, all P < 0.01). Under this condition, collagen type IV secreted into the culture medium was lowered markedly upon the induction of CTGF (P < 0.01). RT-PCR analysis showed that the CTGF gene expression was upregulated by TGF-beta1 stimulation and peaked in 3 hours, and the alpha-SMA expression was upregulated by TGF-beta1 stimulation, however, peaked in 6 hours. The CTGF mRNA expression of the HKC cells transfected with CTGF ASODN that was stimulated by TGF-beta1 10 microg/L was significantly suppressed (P < 0.01) and the alpha-SMA mRNA expression induced by TGF-beta1 10 microg/L was significantly inhibited by CTGF ASODN transfection (P < 0.01). Indirect immunofluorescence assay showed that normal HKC cells did not express alpha-SMA, 48 hours after stimulation of TGF-beta1 10 microg/L the HKC cells showed expression of alpha-SMA in the cytoplasm, and the intracytoplasmic alpha-SMA expression was significantly down-regulated by the transfection of CTGF ASODN (P < 0.01). CONCLUSION: CTGF can promote the transdifferentiation of human renal tubular epithelial cells towards myofibroblast (MyoF) in vitro, and CTGF blockade results in a dramatic inhibition of TGF-beta-induced transdifferentiation of renal tubular cells. So CTGF may be a crucial factor in promoting tubular-epithelial myofibroblast transdifferentiation.

Actins↗

Reconstruction of chemically burned rat corneal surface by bone marrow-derived human mesenchymal stem cells.

To examine whether transplantation of human mesenchymal stem cells (MSCs) could reconstruct the corneal damage and also whether grafted MSCs could differentiate into corneal epithelial cells, we isolated MSCs from healthy donors. After growth and expansion on amniotic membrane, cells were transplanted into rat corneas 7 days after chemical burns. Reconstruction of the damaged cornea and the rat vision were measured once a week by slit lamp and by an optokinetic head-tracking instrument, respectively. Corneas were then cut out, fixed, and imbedded for immunofluorescent study of the expression of keratin 3 and keratin-pan as epithelial cell markers. Expression of CD45, interleukin 2, and metalloproteinase-2 was also investigated for inflammation and inflammation-related angiogenesis. The data showed that transplantation of MSCs, like limbal epithelial stem cells, successfully reconstructed damaged rat corneal surface. Interestingly, the therapeutic effect of the transplantation may be associated with the inhibition of inflammation and angiogenesis after transplantation of MSCs rather than the epithelial differentiation from MSCs. This study provides the first line of evidence that MSCs can be used for reconstruction of damaged corneas, presenting a new source for autotransplantation in the treatment of corneal disorders.

Animals↗

Experimental and theoretical investigation of single Cu, Ag, and Au atoms adsorbed on Si(111)-(7x7).

Using scanning tunneling microscopy and first principles calculations, the adsorption sites of single Cu, Ag, and Au atoms on the Si(111)-(7x7) surface have been systematically investigated and identified. Despite their monovalence, these atoms were found to adsorb at high coordination sites, seeking to saturate the maximum number of dangling bonds. The stable adsorption sites were further observed to be distinctly different in the faulted and unfaulted half unit cells, showing an asymmetry that has never been observed for many other adsorbates.

Journal Article↗

Time-dependent tunneling spectroscopy for studying surface diffusion confined in nanostructures.

By confining a diffusion atom in a nanometer region using surface potential heterogeneity, we have successfully employed a time-dependent tunneling spectroscopy to quantitatively study its random motion. A hopping rate in the range of 1-10(4) Hz, approximately 3 orders of magnitude faster than those accessible by the existing diffusion methods based on scanning tunneling microscopy, was demonstrated for single Cu atoms diffusing in the faulted half unit cell of Si(111)-(7 x 7). Our technique is potentially useful to detect fast diffusion processes such as H quantum diffusion at atomic scale.

Journal Article↗

Co-immunoprecipitation of Hsp101 with cytosolic Hsc70.

In animals and yeast, cytosolic Hsp70s function in concert with other molecular chaperones. Hsp70 is a major chaperone in the Hsp90 multi-chaperone complexes that participate in maturation of steroid receptors and several other proteins. Hsp70s also appear to form a complex with Hsp90 and Hsp110/sHsp. A 100 kDa protein was co-immunoprecipitated with cytosolic Hsc70 from maize seedlings (Zea mays). The presence of this complex was further confirmed using gel-filtration chromatography. Mass spectrometric analysis showed that the 100 kDa protein is homologous with Arabidopsis Hsp101. Treatment with apyrase enhanced the co-immunoprecipitation of Hsp101 with Hsc70, while ATP had the opposite effect. In the presence of carboxymethylated alpha-lactalbumin (CMLA), which is permanently unfolded, the complex dissociated. Based on these observations, it is concluded that Hsc70 and Hsp101 are present in a complex in the plant cytosol.

Adenosine Triphosphate↗

Expression of connective tissue growth factor in renal tubulointerstitial fibrosis in rats and its pathogenic role.

In order to explore the role of connective tissue growth factor (CTGF) in the pathogenesis of renal tubulointerstitial fibrosis, 48 Wistar rats were randomly divided into sham-operated and unilateral ureteral obstruction (UUO) group. On the postoperative day 1, 3, 7 and 14, the rats were killed and the kidneys were removed. The renal tubulointerstitial injury index was evaluated according to the MASSON staining. The mRNA levels of CTGF, transforming growth factor-beta1 (TGF-beta1), collagen I (col I), and plasminogen activator inhibitor-1 (PAI-1) were detected using reverse transcriptional-polymerase chain reaction (RT-PCR). Immunohistochemistry was performed to evaluate the protein expression of the above factors, and the relations among them were analyzed. Quantitative expression of CTGF protein in the kidneys was also assessed using Western blot. The results showed that TGF-beta1 mRNA level was increased at first day after UUO, followed by a marked elevation of CTGF mRNA level, which began to increase 3 days after UUO (P < 0.01). With the progression of the disease, the mRNA expression of CTGF, col I and PAI-1 was increased progressively. Immunohistochemistry revealed that the CTGF protein expression was significantly increased in fibrotic areas and tubular epithelial cells 3 days after UUO. On the post-UUO day 7, the protein level of CTGF was positively related to the renal tubulointerstitial injury index (r = 0.62, P < 0.01), the expression of TGF-beta1 (r = 0.85, P < 0.01), col I (r = 0.78, P < 0.01), and PAI-1 (r = 0.76, P < 0.01). Upon Western blot analysis, CTGF protein expression began to increase 3 days after UUO, and appeared progressively throughout the time course (P < 0.01, as compared with sham-operated group). It is concluded that CTGF can be induced by TGF-beta and mediate various profibrotic actions of this cytokine, such as increasing extracellular matrix (ECM) synthesis and decreasing ECM degradation. The increased expression of CTGF may play a crucial role in the development and progression of tubulointerstitial fibrosis.

Animals↗

Expression of serum and glucocorticoid-inducible kinase1 in diabetic rats and its modulation by fluvastatin.

The expression of serum and glucocorticoid-induced protein kinase in the renal cortex of diabetic rats was examined, and the function of signal transduction mediated by SGK1 in diabetic nephropathy and its modulatiqn by fluvastatin were also investigated. 24 male Wistar rats were randomly divided into normal control group (n = 8), diabetic nephropathy group (n = 8) and fluvastatin-treated diabetic nephropathy group (15 mg/kg/d, n = 8). The metabolic parameters were measured at the 8th week. The expression of transforming growth factor beta1 (TGF-beta1) and fibronectin (FN) was immunohistochemically examined. The expression of SGK1 was detected by RT-PCR and Western blot, and CTGF mRNA was assessed by RT-PCR. As compared to DN, blood glucose, 24-h urinary protein, Cer and kidney weight index were all decreased and the weight was increased obviously in group F. At the same time, mesangial cells and extracellular matrix proliferation were relieved significantly. The levels of cortex SGK1 mRNA and protein were up-regulated, and both TGF-beta1 and FN were down-regulated by fluvastatin. The mRNA of SGK1 was positively correlated with the CTGF, TGF-beta1 and FN. SGK1 expression is markedly up-regulated in the renal cortex of DN group and plays an important role in the development and progress of diabetic nephropathy by means of signal transduction. Fluvastatin suppressed the increased SGK1mRNA expression in renal cortex and postponed the development of diabetic nephropathy.

Animals↗